In short
Donepezil hydrochloride monohydrate is a chemically synthesised acetylcholinesterase inhibitor, already authorised as a medicine for dementia of the Alzheimer's type. It is currently being studied in a Phase 2 trial for anorexia nervosa, with 147 participants planned. The trial is authorised and compares donepezil given by mouth with placebo over 90 days.
Key points
- Donepezil hydrochloride monohydrate is an acetylcholinesterase inhibitor authorised for Alzheimer's disease.
- One Phase 2 trial is studying donepezil in anorexia nervosa.
- The trial plans to enrol 147 participants and is currently authorised.
- Participants receive donepezil as 2.5 mg or 5 mg film-coated tablets by mouth.
- The main outcome is the change in EDE-Q score between day 0 and day 90.
- The trial is a multicentre double-blind randomised controlled trial versus placebo.
What is donepezil hydrochloride monohydrate?
Donepezil hydrochloride monohydrate is a chemically synthesised substance classified as an acetylcholinesterase inhibitor (ATC code N06DA02). It is already authorised as a medicine in France, where it is supplied under product names including ARICEPT 5 mg, DONEPEZIL ARROW 5 mg and DONEPEZIL BIOGARAN 5 mg, all as film-coated tablets. The authorisation holders include GROUPE HOSPITALIER UNIVERSITAIRE PARIS PSYCHIATRIE & NEUROSCIENCE, ARROW GENERIQUES and EISAI S.A.S. In the United States, donepezil hydrochloride tablets received initial approval in 1996 for the treatment of dementia of the Alzheimer's type.
How does donepezil hydrochloride monohydrate work?
Donepezil is a selective and reversible inhibitor of the enzyme acetylcholinesterase. By blocking this enzyme, donepezil slows the breakdown of acetylcholine, a chemical messenger in the brain. This increases the amount of acetylcholine available at nerve endings, which is thought to help maintain cognitive function in conditions where cholinergic signalling is reduced. The rationale for studying donepezil in anorexia nervosa is that acetylcholine pathways may also be involved in the repetitive and compulsive behaviours seen in the condition.
Which conditions is donepezil used or studied for?
- Dementia of the Alzheimer's type — donepezil is authorised for this condition, with efficacy demonstrated in mild, moderate and severe Alzheimer's disease.
- Anorexia nervosa — donepezil is being investigated in a Phase 2 trial to evaluate whether it can improve the symptomatology of anorexia nervosa compared with placebo.
How is donepezil hydrochloride monohydrate given?
Donepezil hydrochloride monohydrate is given by mouth. In the registered trials, the pharmaceutical forms are film-coated tablets and capsules. In the anorexia nervosa trial, participants receive donepezil as 2.5 mg or 5 mg film-coated tablets taken orally. For Alzheimer's disease, the product information gives a 5 mg to 10 mg once-daily oral dose for mild to moderate disease, and 10 mg to 23 mg once daily for moderate to severe disease.
What do the clinical trials show?
One clinical trial is registered for donepezil hydrochloride monohydrate in anorexia nervosa. It is a Phase 2, multicentre, double-blind, randomised controlled trial comparing donepezil with placebo. The trial is currently authorised and plans to enrol 147 participants. The main outcome measure is the absolute intra-individual difference in the total EDE-Q score between inclusion at day 0 and day 90. The EDE-Q, or Eating Disorder Examination Questionnaire, is a self-report measure of eating disorder symptoms; a larger change in score would indicate a greater improvement in symptomatology.
The trial does not yet have published results, so it is too early to say whether donepezil improves anorexia nervosa symptoms. The authorised status means the trial has received regulatory approval to begin recruiting participants.
Who can take part in the anorexia nervosa trial?
The registered trial record does not detail the specific inclusion and exclusion criteria for participants. The trial is described as a multicentre study, meaning it takes place at more than one hospital or clinic. The condition under study is anorexia nervosa, so participants are expected to be people diagnosed with this condition. The trial compares donepezil given by mouth with a placebo that has the same container composition as the investigational medicinal product, except for the active substance.
What side effects are known?
According to the US prescribing information, cholinesterase inhibitors such as donepezil may have vagotonic effects on the sinoatrial and atrioventricular nodes of the heart, manifesting as bradycardia (slow heart rate) or heart block. Donepezil can cause vomiting, and patients should be observed closely at initiation of treatment and after dose increases. The use of donepezil at a dose of 23 mg once daily is associated with weight loss. Cholinomimetics may cause bladder outflow obstructions, and patients should be monitored closely for symptoms of active or occult gastrointestinal bleeding, especially those at increased risk for developing ulcers. Cholinesterase inhibitors are likely to exaggerate succinylcholine-type muscle relaxation during anaesthesia.